The goal of this proposal is to extend the scope of our on-going studies to test specific hypotheses regarding the effects of maternal-placental-fetal stress biology during intrauterine life on the human newborn and infant telomere biology system. The elucidation of biological mechanisms underlying the effects of the intrauterine environment on subsequent health and disease risk outcomes (fetal/developmental programming) is an area of active interest and intense investigation. We advance the hypothesis that telomere biology may represent an important and novel mechanism underlying the observed effects of disparate suboptimal intrauterine exposures on subsequent health and disease risk phenotypes of interest. We propose to focus on two key telomere biology-related outcomes - leukocyte telomere length at birth and at 12 months age, and mitogen-stimulated leukocyte telomerase expression at birth, and on the effects of a major biological pathway in human gestation - stress-related maternal-placental-fetal (MPF) endocrine, immune/inflammatory and oxidative state - that may mediate the effects of a diverse set of suboptimal conditions on the developing fetus. We will conduct a prospective, longitudinal, follow-up study in a representative, population-based cohort of N=120 newborns from birth (T1) and over the early postnatal growth phase until 12 months age (T2). A unique strength of our proposal is the availability in our parent projects (RO1 HD-060628, RO1 HD-065825) of a cohort of newborns and infants who are extensively characterized over the course of intrauterine and postnatal life with the measures required in the present study. Another notable feature includes our trans-disciplinary team of investigators with a collaboration record and extensive, published expertise in maternal-placental-fetal stress biology (Pathik Wadhwa, Sonja Entringer), telomere biology (Elizabeth Blackburn, Elissa Epel, Jue Lin), immunology (Edward Nelson), and obstetrics/neonatology (Deborah Wing, Hyagriv Simhan). We will address the following Specific Aims: 1) To test the hypothesis that exposure to elevated intrauterine biological stress predicts a) newborn leukocyte telomere length (LTL) and b) change in LTL from birth till 12 months age. 2) To test the hypothesis that exposure to elevated intrauterine biological stress predicts newborn leukocyte telomerase activity. 3) After identifying which measures of intrauterine stress biology (and at which specific time points in gestation) predict newborn and infant LTL and telomerase activity, we will address exploratory questions of their determinants using the available comprehensive data collected in the on-going parent projects. The significance and impact of this study derives from the importance of achieving at a better understanding of underlying processes (mechanisms) that alter risk or vulnerability for subsequent health and disease risk outcomes. This study will collect novel data (serial measures of newborn and infant telomere biology) and address hypotheses that set the stage for translational research. We submit that this proposed study represents an appropriate expansion of the scientific scope of the parent project.